Pretreatment of the human colon carcinoma cell line, HT-29, with IFN-G increases their vulnerability to lysis by unactivated monocytes. Because we had previously observed the importance of certain adhesion molecules on monocyte-mediated cytotoxicity, we wanted to determine if this activity was due to changes in the expression of ICAM-1 on the tumor cells. HT-29 cells expressed low levels of ICAM-1 and this expression was dramatically increased ( greater than 150%) by IFN-gamma or TNF treatment. IFN-alpha, IL-1 and GM-CSF treatment, however, had only marginal effects on ICAM-1 expression. Likewise, when HT-29 cells were pretreated with IFN-gamma or TNF, the monocyte-mediated cytotoxicity of these cells was significantly increased, while pretreatment with IFN-alpha, IL-1 or GM-CSF had no effect. While anti-ICAM-1 antibodies did not inhibit the 10-20% baseline killing of the untreated HT-29 cells, the anti-ICAM-1 antibodies did inhibit the augmented killing of the HT-29 cells observed following IFN-gamma or TNF pretreatment. Thus, certain cytokines can increase the expression of ICAM-1 on tumor cells thereby increasing their sensitivity to lysis by monocytes.